LOCUS       NM_016123               4284 bp    mRNA    linear   PRI 02-APR-2024
DEFINITION  Homo sapiens interleukin 1 receptor associated kinase 4 (IRAK4),
            transcript variant 2, mRNA.
ACCESSION   NM_016123
VERSION     NM_016123.4
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 4284)
  AUTHORS   Peterson,J., Balogh Sivars,K., Bianco,A. and Roper,K.
  TITLE     Toll-like receptor signalling via IRAK4 affects epithelial
            integrity and tightness through regulation of junctional tension
  JOURNAL   Development 150 (24) (2023)
   PUBMED   37997696
  REMARK    GeneRIF: Toll-like receptor signalling via IRAK4 affects epithelial
            integrity and tightness through regulation of junctional tension.
REFERENCE   2  (bases 1 to 4284)
  AUTHORS   Bennett,J., Ishikawa,C., Agarwal,P., Yeung,J., Sampson,A.,
            Uible,E., Vick,E., Bolanos,L.C., Hueneman,K., Wunderlich,M.,
            Kolt,A., Choi,K., Volk,A., Greis,K.D., Rosenbaum,J., Hoyt,S.B.,
            Thomas,C.J. and Starczynowski,D.T.
  TITLE     Paralog-specific signaling by IRAK1/4 maintains MyD88-independent
            functions in MDS/AML
  JOURNAL   Blood 142 (11), 989-1007 (2023)
   PUBMED   37172199
  REMARK    GeneRIF: Paralog-specific signaling by IRAK1/4 maintains
            MyD88-independent functions in MDS/AML.
REFERENCE   3  (bases 1 to 4284)
  AUTHORS   Cooray,S., Price-Kuehne,F., Hong,Y., Omoyinmi,E., Burleigh,A.,
            Gilmour,K.C., Ahmad,B., Choi,S., Bahar,M.W., Torpiano,P.,
            Gagunashvili,A., Jensen,B., Bellos,E., Sancho-Shimizu,V.,
            Herberg,J.A., Mankad,K., Kumar,A., Kaliakatsos,M., Worth,A.J.J.,
            Eleftheriou,D., Whittaker,E. and Brogan,P.A.
  TITLE     Neuroinflammation, autoinflammation, splenomegaly and anemia caused
            by bi-allelic mutations in IRAK4
  JOURNAL   Front Immunol 14, 1231749 (2023)
   PUBMED   37744344
  REMARK    GeneRIF: Neuroinflammation, autoinflammation, splenomegaly and
            anemia caused by bi-allelic mutations in IRAK4.
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 4284)
  AUTHORS   Garcia-Garcia,A., Perez de Diego,R., Flores,C., Rinchai,D.,
            Sole-Violan,J., Deya-Martinez,A., Garcia-Solis,B.,
            Lorenzo-Salazar,J.M., Hernandez-Brito,E., Lanz,A.L., Moens,L.,
            Bucciol,G., Almuqamam,M., Domachowske,J.B., Colino,E.,
            Santos-Perez,J.L., Marco,F.M., Pignata,C., Bousfiha,A.,
            Turvey,S.E., Bauer,S., Haerynck,F., Ocejo-Vinyals,J.G.,
            Lendinez,F., Prader,S., Naumann-Bartsch,N., Pachlopnik Schmid,J.,
            Biggs,C.M., Hildebrand,K., Dreesman,A., Cardenes,M.A., Ailal,F.,
            Benhsaien,I., Giardino,G., Molina-Fuentes,A., Fortuny,C.,
            Madhavarapu,S., Conway,D.H., Prando,C., Schidlowski,L., Martinez de
            Saavedra Alvarez,M.T., Alfaro,R., Rodriguez de Castro,F., Meyts,I.,
            Hauck,F., Puel,A., Bastard,P., Boisson,B., Jouanguy,E., Abel,L.,
            Cobat,A., Zhang,Q., Casanova,J.L., Alsina,L. and
            Rodriguez-Gallego,C.
  CONSRTM   ESID Registry Working Party; COVID Human Genetic Effort
  TITLE     Humans with inherited MyD88 and IRAK-4 deficiencies are predisposed
            to hypoxemic COVID-19 pneumonia
  JOURNAL   J Exp Med 220 (5) (2023)
   PUBMED   36880831
  REMARK    GeneRIF: Humans with inherited MyD88 and IRAK-4 deficiencies are
            predisposed to hypoxemic COVID-19 pneumonia.
REFERENCE   5  (bases 1 to 4284)
  AUTHORS   Wang,Z., Liu,J., Sudom,A., Ayres,M., Li,S., Wesche,H., Powers,J.P.
            and Walker,N.P.
  TITLE     Crystal structures of IRAK-4 kinase in complex with inhibitors: a
            serine/threonine kinase with tyrosine as a gatekeeper
  JOURNAL   Structure 14 (12), 1835-1844 (2006)
   PUBMED   17161373
  REMARK    GeneRIF: crystallographic analysis of IRAK-4 kinase in complex with
            inhibitors
REFERENCE   6  (bases 1 to 4284)
  AUTHORS   Suzuki,N. and Saito,T.
  TITLE     IRAK-4--a shared NF-kappaB activator in innate and acquired
            immunity
  JOURNAL   Trends Immunol 27 (12), 566-572 (2006)
   PUBMED   17046325
  REMARK    GeneRIF: Although each system seems to possess distinct activation
            mechanisms, interleukin-1 receptor-associated kinase (IRAK)-4 is
            essential for NF-kappaB activation in Toll-like receptor (TLR) and
            T-cell receptor (TCR) signaling pathways.
            Review article
REFERENCE   7  (bases 1 to 4284)
  AUTHORS   Suzuki,N., Suzuki,S., Duncan,G.S., Millar,D.G., Wada,T.,
            Mirtsos,C., Takada,H., Wakeham,A., Itie,A., Li,S., Penninger,J.M.,
            Wesche,H., Ohashi,P.S., Mak,T.W. and Yeh,W.C.
  TITLE     Severe impairment of interleukin-1 and Toll-like receptor
            signalling in mice lacking IRAK-4
  JOURNAL   Nature 416 (6882), 750-756 (2002)
   PUBMED   11923871
REFERENCE   8  (bases 1 to 4284)
  AUTHORS   Burns,K., Clatworthy,J., Martin,L., Martinon,F., Plumpton,C.,
            Maschera,B., Lewis,A., Ray,K., Tschopp,J. and Volpe,F.
  TITLE     Tollip, a new component of the IL-1RI pathway, links IRAK to the
            IL-1 receptor
  JOURNAL   Nat Cell Biol 2 (6), 346-351 (2000)
   PUBMED   10854325
REFERENCE   9  (bases 1 to 4284)
  AUTHORS   Scanlan,M.J., Gordan,J.D., Williamson,B., Stockert,E., Bander,N.H.,
            Jongeneel,V., Gure,A.O., Jager,D., Jager,E., Knuth,A., Chen,Y.T.
            and Old,L.J.
  TITLE     Antigens recognized by autologous antibody in patients with
            renal-cell carcinoma
  JOURNAL   Int J Cancer 83 (4), 456-464 (1999)
   PUBMED   10508479
REFERENCE   10 (bases 1 to 4284)
  AUTHORS   Siu,G., Strauss,E.C., Lai,E. and Hood,L.E.
  TITLE     Analysis of a human V beta gene subfamily
  JOURNAL   J Exp Med 164 (5), 1600-1614 (1986)
   PUBMED   3772297
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AK304583.1, AK314288.1,
            BC013316.1, AC093012.9 and AI126481.1.
            
            On Dec 4, 2019 this sequence version replaced NM_016123.3.
            
            Summary: This gene encodes a kinase that activates NF-kappaB in
            both the Toll-like receptor (TLR) and T-cell receptor (TCR)
            signaling pathways. The protein is essential for most innate immune
            responses. Mutations in this gene result in IRAK4 deficiency and
            recurrent invasive pneumococcal disease. Multiple transcript
            variants encoding different isoforms have been found for this gene.
            [provided by RefSeq, Aug 2011].
            
            Transcript Variant: This variant (2) differs in the 5' UTR compared
            to variant 1. Variants 1, 2, and 13 all encode the same isoform
            (a).
            
            Sequence Note: This RefSeq record was created from transcript and
            genomic sequence data to make the sequence consistent with the
            reference genome assembly. The genomic coordinates used for the
            transcript record were based on transcript alignments.
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: AK000528.1, AF155118.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000613694.5/ ENSP00000479889.3
            RefSeq Select criteria :: based on manual assertion, conservation,
                                      expression, longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-4                 AK304583.1         11-14
            5-366               AK314288.1         1-362
            367-1610            BC013316.1         362-1605
            1611-3886           AC093012.9         53819-56094
            3887-4284           AI126481.1         13-410              c
FEATURES             Location/Qualifiers
     source          1..4284
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="12"
                     /map="12q12"
     gene            1..4284
                     /gene="IRAK4"
                     /gene_synonym="IMD67; IPD1; IRAK-4; NY-REN-64; REN64"
                     /note="interleukin 1 receptor associated kinase 4"
                     /db_xref="GeneID:51135"
                     /db_xref="HGNC:HGNC:17967"
                     /db_xref="MIM:606883"
     exon            1..66
                     /gene="IRAK4"
                     /gene_synonym="IMD67; IPD1; IRAK-4; NY-REN-64; REN64"
                     /inference="alignment:Splign:2.1.0"
     exon            67..236
                     /gene="IRAK4"
                     /gene_synonym="IMD67; IPD1; IRAK-4; NY-REN-64; REN64"
                     /inference="alignment:Splign:2.1.0"
     CDS             76..1458
                     /gene="IRAK4"
                     /gene_synonym="IMD67; IPD1; IRAK-4; NY-REN-64; REN64"
                     /EC_number="2.7.11.1"
                     /note="isoform a is encoded by transcript variant 2; renal
                     carcinoma antigen NY-REN-64"
                     /codon_start=1
                     /product="interleukin-1 receptor-associated kinase 4
                     isoform a"
                     /protein_id="NP_057207.2"
                     /db_xref="CCDS:CCDS8744.1"
                     /db_xref="GeneID:51135"
                     /db_xref="HGNC:HGNC:17967"
                     /db_xref="MIM:606883"
                     /translation="MNKPITPSTYVRCLNVGLIRKLSDFIDPQEGWKKLAVAIKKPSG
                     DDRYNQFHIRRFEALLQTGKSPTSELLFDWGTTNCTVGDLVDLLIQNEFFAPASLLLP
                     DAVPKTANTLPSKEAITVQQKQMPFCDKDRTLMTPVQNLEQSYMPPDSSSPENKSLEV
                     SDTRFHSFSFYELKNVTNNFDERPISVGGNKMGEGGFGVVYKGYVNNTTVAVKKLAAM
                     VDITTEELKQQFDQEIKVMAKCQHENLVELLGFSSDGDDLCLVYVYMPNGSLLDRLSC
                     LDGTPPLSWHMRCKIAQGAANGINFLHENHHIHRDIKSANILLDEAFTAKISDFGLAR
                     ASEKFAQTVMTSRIVGTTAYMAPEALRGEITPKSDIYSFGVVLLEIITGLPAVDEHRE
                     PQLLLDIKEEIEDEEKTIEDYIDKKMNDADSTSVEAMYSVASQCLHEKKNKRPDIKKV
                     QQLLQEMTAS"
     exon            237..382
                     /gene="IRAK4"
                     /gene_synonym="IMD67; IPD1; IRAK-4; NY-REN-64; REN64"
                     /inference="alignment:Splign:2.1.0"
     exon            383..565
                     /gene="IRAK4"
                     /gene_synonym="IMD67; IPD1; IRAK-4; NY-REN-64; REN64"
                     /inference="alignment:Splign:2.1.0"
     exon            566..726
                     /gene="IRAK4"
                     /gene_synonym="IMD67; IPD1; IRAK-4; NY-REN-64; REN64"
                     /inference="alignment:Splign:2.1.0"
     exon            727..791
                     /gene="IRAK4"
                     /gene_synonym="IMD67; IPD1; IRAK-4; NY-REN-64; REN64"
                     /inference="alignment:Splign:2.1.0"
     exon            792..906
                     /gene="IRAK4"
                     /gene_synonym="IMD67; IPD1; IRAK-4; NY-REN-64; REN64"
                     /inference="alignment:Splign:2.1.0"
     exon            907..1016
                     /gene="IRAK4"
                     /gene_synonym="IMD67; IPD1; IRAK-4; NY-REN-64; REN64"
                     /inference="alignment:Splign:2.1.0"
     exon            1017..1200
                     /gene="IRAK4"
                     /gene_synonym="IMD67; IPD1; IRAK-4; NY-REN-64; REN64"
                     /inference="alignment:Splign:2.1.0"
     exon            1201..1263
                     /gene="IRAK4"
                     /gene_synonym="IMD67; IPD1; IRAK-4; NY-REN-64; REN64"
                     /inference="alignment:Splign:2.1.0"
     exon            1264..1422
                     /gene="IRAK4"
                     /gene_synonym="IMD67; IPD1; IRAK-4; NY-REN-64; REN64"
                     /inference="alignment:Splign:2.1.0"
     exon            1423..4284
                     /gene="IRAK4"
                     /gene_synonym="IMD67; IPD1; IRAK-4; NY-REN-64; REN64"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2813..2818
                     /regulatory_class="polyA_signal_sequence"
                     /gene="IRAK4"
                     /gene_synonym="IMD67; IPD1; IRAK-4; NY-REN-64; REN64"
                     /note="hexamer: AATAAA"
     polyA_site      2831
                     /gene="IRAK4"
                     /gene_synonym="IMD67; IPD1; IRAK-4; NY-REN-64; REN64"
                     /note="major polyA site"
     regulatory      4264..4269
                     /regulatory_class="polyA_signal_sequence"
                     /gene="IRAK4"
                     /gene_synonym="IMD67; IPD1; IRAK-4; NY-REN-64; REN64"
                     /note="hexamer: ATTAAA"
     polyA_site      4284
                     /gene="IRAK4"
                     /gene_synonym="IMD67; IPD1; IRAK-4; NY-REN-64; REN64"
                     /note="major polyA site"
ORIGIN      
        1 cttcgcggcg cttcctagtt cggctggttc ttctgtcgcc ggcttcagca gcccgcgccc
       61 gggcaggaat agaagatgaa caaacccata acaccatcaa catatgtgcg ctgcctcaat
      121 gttggactaa ttaggaagct gtcagatttt attgatcctc aagaaggatg gaagaagtta
      181 gctgtagcta ttaaaaaacc atctggtgat gatagataca atcagtttca cataaggaga
      241 tttgaagcat tacttcaaac tggaaaaagt cccacttctg aattactgtt tgactggggc
      301 accacaaatt gcacagttgg tgatcttgtg gatcttttga tccaaaatga attttttgct
      361 cctgcgagtc ttttgctccc agatgctgtt cccaaaactg ctaatacact accttctaaa
      421 gaagctataa cagttcagca aaaacagatg cctttctgtg acaaagacag gacattgatg
      481 acacctgtgc agaatcttga acaaagctat atgccacctg actcctcaag tccagaaaat
      541 aaaagtttag aagttagtga tacacgtttt cacagttttt cattttatga attgaagaat
      601 gtcacaaata actttgatga acgacccatt tctgttggtg gtaataaaat gggagaggga
      661 ggatttggag ttgtatataa aggctacgta aataacacaa ctgtggcagt gaagaagctt
      721 gcagcaatgg ttgacattac tactgaagaa ctgaaacagc agtttgatca agaaataaaa
      781 gtaatggcaa agtgtcaaca tgaaaactta gtagaactac ttggtttctc aagtgatgga
      841 gatgacctct gcttagtata tgtttacatg cctaatggtt cattgctaga cagactctct
      901 tgcttggatg gtactccacc actttcttgg cacatgagat gcaagattgc tcagggtgca
      961 gctaatggca tcaattttct acatgaaaat catcatattc atagagatat taaaagtgca
     1021 aatatcttac tggatgaagc ttttactgct aaaatatctg actttggcct tgcacgggct
     1081 tctgagaagt ttgcccagac agtcatgact agcagaattg tgggaacaac agcttatatg
     1141 gcaccagaag ctttgcgtgg agaaataaca cccaaatctg atatttacag ctttggtgtg
     1201 gttttactag aaataataac tggacttcca gctgtggatg aacaccgtga acctcagtta
     1261 ttgctagata ttaaagaaga aattgaagat gaagaaaaga caattgaaga ttatattgat
     1321 aaaaagatga atgatgctga ttccacttca gttgaagcta tgtactctgt tgctagtcaa
     1381 tgtctgcatg aaaagaaaaa taagagacca gacattaaga aggttcaaca gctgctgcaa
     1441 gagatgacag cttcttaaaa ctttattgga aaagactctt gactttttat atacacctat
     1501 ctcaaccatt tttttaactg atttttttcc taaatattct tctttacctt taacaaggca
     1561 taggctgttg caggacagtg gttattaaag catgggttga acttccaaaa tataaaaata
     1621 gagccaccat atcaacactt agccctaccc attagtatca cccccagttc ttacagtaat
     1681 ccctgagaaa tctccttcaa gcatcaccaa acacagtttg aaaattacag ggttagcaaa
     1741 aagagcctgg gctgtatgta gggtggaaac actctgatct gaagcccagc tgactccact
     1801 actaatttgc tgtaaagctt tggacataca cttagctgct gtgagccact aataacattg
     1861 ggctaatatc tgctgtgctt ctctgacagg tagtcatgaa aatcaaatga tgcaaaatat
     1921 atacaagcac tttgtaaatt gtaaaatgat acaaaattta aagtttatag agccagttac
     1981 aaaatcctat tagtcatata tttatagatt gtgttcacag caatcattta accacaaata
     2041 aaatatccct tgatgatact gccataatga tatgtccatt attagattat gttacatgac
     2101 aaagttgaag gaatttggca gatgcagtta aggttcctaa acaactcact ttgagactgt
     2161 tgaaagggcc tgacctaatc aagtgaaccc ttgcaagaag aattctcctt gtaagccttg
     2221 aagaagtatg tgagagggcc acattggcta aaacctaaag gtggcctcta ggagatgaga
     2281 cctaccttcc agttgtcagc aagcaggaaa aaaaaattgg gacctcagtt gcaaccacaa
     2341 ggaactgaat tctgccaaaa atctgagtca gcttagaaga gtactccaag cttcagatga
     2401 taaccacagc ctgggctgac acctggattt cagctttgca tgatcctcag tatgagaatc
     2461 tatctgttct gtgctggact tctaatatat agaactgtga gataatgggt cacattggct
     2521 ggatgtggtg gctcatacct gtaaatccca gcactttggg aggccgaggc aggcagatca
     2581 cctgaggtca agagttcaag accggcctgg ccaacatggt gaaaccccgt ctctactaaa
     2641 aatacaaaaa ttagacgagc gtggtggtgg acacctgtag tcccagctac ttgggaggct
     2701 gaggcaggag actagctgga accagggagg tagaggttgc agtgagctga gatcgtgcca
     2761 ctgcactcca gcctgggtga cagagtgaga ctccatcata aataaataaa taaataaatg
     2821 ggtcacatta agcctttaag tttgtggtaa tttattattc agtaatagaa aacaaataca
     2881 gatactctcc catgatgttt ttcccatgat gatttcccat gatatttaca ggttttgccc
     2941 acatttgagg ggtatgtgga aattatacag agcatgtaca gcgggaggct tatagtgtac
     3001 gtactgaaat gtggggttgg agccccaaca cagagacccc agcaggacac tgcctagtag
     3061 agctatggga agggtgctgc caccctccag acttgagaat tgtagagcca ccagcagctt
     3121 gcactctgag cttggaaaag ccacaggcac tcaacttcaa ccatgaggga agccacgcac
     3181 cctgcaaagc cacaggagtg gagctgccca cggcctcgag ggcccacccc ttgcaccagt
     3241 gtgccaggat gtgggacatg gaatcaagga atatgttagg gctttttttt tttttttttt
     3301 gagacggagt cttgctctgt tgcccaggct ggagtgcagt ggcacgatct cggctcactg
     3361 caagctctgc ctcccaggtt cacgccattc ccctgcctca gcctccccag tagctgggac
     3421 tacaggtgcc cgccaccatg cccagctaat tttttttgta tttttagtag agatggggtt
     3481 tcactgtgtt agccaggatg gtcttgatct cctgacctcg tgatcacccg cctcggcctc
     3541 ccaaagtgcc agtatttaaa gtttaatgtc ttcccagctg ggtttcagac ttgccaggat
     3601 cctgttgccc ctttctttag ccaatttctc ccttttggga caagaatgtt ttacttattg
     3661 cctgtaccac caactgtatc ttggaaataa ataacttata ttttatttca gaggctcata
     3721 ggcggcagga acttaccttg agtctcaaat gagacttagg acttttgagt gatgctagaa
     3781 tgagttaaga ctttgggaag ggatgattat attttgcaat gtgagaaaga cattagattt
     3841 ggggggctgg gggtagaatg acattgttta gatgtttgtc tccttcaaat ttcatgttta
     3901 aatgtaatcc ccagtgttgg gggtggaggt ggggcctgat gggaagtgtt tgggtcatgg
     3961 tggatgatcc ctcatgaatg gcttagagcc actggtgatg agtgagttct cactcagttc
     4021 gtgtgagatc tggtggctta aaagagtctg ctcccccttt gccttccatt gtgattgtaa
     4081 ccttcctggg gccttcatca aaggccaggc aaatattggt gccgtgctag tatggcctgc
     4141 agaaccgtaa gccaaaacaa accttttttc tttataaatt acccagcctc agttattcct
     4201 ttatagtgat gcaaaacggg ctaactatat aaatttgtaa tttttaagtt atagattgtt
     4261 tttattaaac acttatgaat actg
//
